Oral delivery of many compounds, natural or synthetic, generally results in limited bioavailability, and thus often requires large doses of the compounds in order to achieve efficacy. Bolus doses of many such compounds though are not feasible in humans due to toxicity concerns or due to the unavailability of compounds. Furthermore, some natural compounds, despite being administered in large doses (e.g., curcumin), have still resulted in limited bioavailability in pre-clinical and clinical studies due to poor absorption and rapid hepatic metabolism. On the other hand, chemotherapeutic agents often elicit dose spikes and are highly toxic with severe short-term and long-term side effects. As such, compositions and methods that decrease dose-related toxicities while maintaining drug efficacy are considered to be of great importance.
In this regard, numerous laboratories have attempted to embed or attach certain agents in liposomes, polymer-based formulations, or nanoparticles to improve oral bioavailability. Nevertheless, while these approaches have resulted in some improvements in bioavailability, the carriers themselves, particularly polymer-based nanoparticles, can have toxicity if not cleared effectively. Scalable production of polymer-based and other nanoparticles also continues to be a limitation. Recently, natural nanoparticles, such as exosomes having a size in the range of 30 to 100 nm size, have shown the potential to circumvent problems associated with traditional nanoparticles. However, the ability to effectively encapsulate a specific therapeutic agent or an effective amount of a therapeutic agent in natural nanoparticles, such as an exosomes, has proven difficult in many instances. Additionally, current approaches of isolating exosomes from various body fluids, including milk, are based on differential centrifugation, sucrose-density gradient, Sephadex chromatography, polymer-based (e.g., ExoQuick), and many others. To date though, there are no procedures to isolate natural nanoparticles, such as exosomes or other microvesicles, rapidly and in the bulk quantities required for treating a disease on a commercial level.